Phase 3, Multicenter, Randomized, Open-label Clinical Study of GSK5764227, a B7-H3 Antibody Drug Conjugate (ADC), compared with Topotecan in Participants with Relapsed Small Cell Lung Cancer (SCLC)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Glaxosmithkline Research & Development Limited

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

28 Jan 2026 → ongoing

Decision date (initial)

2025-10-06

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Pharmacodynamic

To compare the antitumor activity of GSK5764227 versus topotecan in participants with relapsed small cell lung cancer (SCLC).

Conditions and MedDRA coding

Neoplasms, Lung

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration, European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. "Has histologically or cytologically confirmed Extensive stage-small cell lung cancer (ES-SCLC). "
2. Has received prior therapy with only one prior platinum-based systemic therapy, given for at least 2 cycles in combination with a Programmed death receptor 1 or programmed death ligand 1 [PD-(L)1] inhibitor,
3. "Has at least 1 non-brain target lesion (TL) per RECIST 1.1, as determined by the investigator "
4. "Has an ECOG performance status of 0 or 1, with no deterioration in the 2 weeks before the first dose. "
5. Has adequate organ function. Screening specimens must be collected at least 3-5 days prior to pre-dose specimens, and pre-dose specimens must be collected within 24 hours prior to first dose.

Exclusion criteria 7

1. "Prior use of or current use of treatments targeting B7 homolog 3 protein (B7-H3). "
2. Has received prior treatment with topoisomerase I inhibitor, including ADC that consists of topoisomerase I inhibitor
3. Pathological diagnosis of complex SCLC (such as mixed SCLC and NSCLC) or transformed SCLC (NSCLC to SCLC).
4. Any evidence of current ILD or pneumonitis or a prior history of ILD or noninfectious pneumonitis requiring high-dose glucocorticoids
5. "Any of the following cardiac examination abnormalities • Has QTc >480 msec. • Evidence of current clinically significant arrhythmias or ECG abnormalities (e.g., complete left bundle branch block, third-degree AV block, second-degree AV block, PR interval >250 msec). • Risk factors of prolonged QTc or arrhythmia events, such as heart failure, refractory hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death of any direct relative under 40 years old or any concomitant medications that prolong the QT interval. • LVEF fraction <50%. "
6. Unresolved toxicity from prior anti-tumor therapy, defined as not having resolved to grade 1 with exceptions defined in the protocol.
7. History of severe hypersensitivity reaction, severe infusion reaction or allergy to recombinant human or mouse derived proteins, DNA topoisomerase I inhibitor or regimens of Topotecan.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. "ORR, defined as the percentage of participants with a confirmed CR or confirmed PR per RECIST 1.1 by BICR assessment "
2. OS, defined as the time from the date of randomization to the date of death by any cause

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Glaxosmithkline Research & Development Limited

Sponsor organisation

Glaxosmithkline Research & Development Limited

Address

79 New Oxford Street

City

London

Postcode

WC1A 1DG

Country

United Kingdom

Scientific contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Public contact point

Organisation

Glaxosmithkline Research & Development Limited

Contact name

EU GSK Clinical Trials Call Center

Third parties 29

Locations

13 EU/EEA countries · 76 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 251 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications